Browsing by Author "Stanojevic, Ivan (55798544900)"

Background: Overproduction of free radicals accompanied with their insufficient removal/neutralization by antioxidative defense system impairs redox hemostasis in living organisms. Oxidative stress has been shown to be involved in all the stages of carcinogenesis and malignant melanocyte transformation. The aim of this study was to examine association between oxidative stress development and different stages of melanoma. Methods: The measured oxidative stress parameters included: superoxide anion radical, total and manganese superoxide dismutase, catalase and malondialdehyde. Oxidative stress parameters were measured spectrophoto- metrically in serum samples from melanoma patients (n=72) and healthy control subjects (n=30). Patients were classified according to AJCC clinical stage. Results: Average superoxide anion and malondialdehyde concentrations were significantly higher in melanoma patients than in control group, with the highest value of superoxide anion in stage III, while malondialdehyde highest value was in stage IV. The activity of total and manganese superoxide dismutase was insignificantly higher in melanoma patients than in control group, while catalase activity was significantly higher. The highest activity of total superoxide dismutase was in stage III, while the highest activity of manganese superoxide dismutase was in stage IV. Catalase activity was increasing with the disease progression achieving the maximum in stage III. Conclusions: Results of our study suggest that melanoma is oxidative stress associated disease, as well as deteriorated cell functioning at mitochondrial level.

Background: Overproduction of free radicals accompanied with their insufficient removal/neutralization by antioxidative defense system impairs redox hemostasis in living organisms. Oxidative stress has been shown to be involved in all the stages of carcinogenesis and malignant melanocyte transformation. The aim of this study was to examine association between oxidative stress development and different stages of melanoma. Methods: The measured oxidative stress parameters included: superoxide anion radical, total and manganese superoxide dismutase, catalase and malondialdehyde. Oxidative stress parameters were measured spectrophoto- metrically in serum samples from melanoma patients (n=72) and healthy control subjects (n=30). Patients were classified according to AJCC clinical stage. Results: Average superoxide anion and malondialdehyde concentrations were significantly higher in melanoma patients than in control group, with the highest value of superoxide anion in stage III, while malondialdehyde highest value was in stage IV. The activity of total and manganese superoxide dismutase was insignificantly higher in melanoma patients than in control group, while catalase activity was significantly higher. The highest activity of total superoxide dismutase was in stage III, while the highest activity of manganese superoxide dismutase was in stage IV. Catalase activity was increasing with the disease progression achieving the maximum in stage III. Conclusions: Results of our study suggest that melanoma is oxidative stress associated disease, as well as deteriorated cell functioning at mitochondrial level.

Background/Aim. Gram-positive and Gram-negative bacteria may induce different inflammatory patterns. The aim of this study was to examine the association of the myeloid-derived suppressor cells (MDSCs) with the type of infecting microorganisms (Gram positive, Gram negative, polymicrobial) and underlying cause of secondary sepsis (peritonitis, pancreatitis, trauma). Methods. Totally, 40 critically ill patients with secondary sepsis were enrolled in the prospective study. Two patients without documented positive blood culture were excluded. We detected and enumerated both main subsets of MDSCs: granulocytic (G)-MDSCs and monocytic (M)-MDSCs on the Days 1 and 5. Blood was simultaneously drawn for a blood culture. The patients with different underlying causes of sepsis (peritonitis, pancreatitis, trauma) were perceived as separated groups and the frequencies and absolute numbers of their G-MDSCs and M-MDSCs were compared. Results. Both main MDSC subpopulations were accumulated significantly in Grampositive sepsis. Univariate logistic regression analyses of investigated variables regarding Gram-positive sepsis on the Day 5 revealed that G-MDSCs absolute number along with both MMDSCs frequency and absolute number had statistically significant power for predicting Gram-positive sepsis. Stepwise multivariate logistic regression analyses of the variables on the Day 5 determined that M-MDSCs absolute number was independent predictor of Gram-positive sepsis [odds ratio (OR) 1.012; p < 0.05]. Clinical accuracy of neutrophil (Ne)/GMDSCs (Ne/G-MDSCs) and monocyte (Mo)/M-MDSCs (Mo/M-MDSCs) ratios in predicting nature of bacteremia and outcome were investigated. Discriminative power of both Ne/G-MDSCs and Mo/M-MDSCs ratios in predicting Grampositive blood culture was statistically significant both on the Day 1 and Day 5 [areas under curve (AUCs): 0.684 and 0.692, and 0.707 and 0.793, respectively). Ne/G-MDSCs both on the Day 1 and Day 5 were statistically significant predictors of lethal outcome (AUCs: 0.694 and 0.678, respectively). There were no statistically significant differences in G-MDSCs and M-MDSCs among different three groups of patients regarding peritonitis, pancreatitis and trauma as causes of sepsis neither on the Day 1 nor on the Day 5. Conclusion. Gram-positive infectious agents were powerful inducers of MDSCs generation in sepsis. Also, underlying causes of secondary sepsis might not seem to influence the MDSCs accumulation. © 2020 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Gal-3 has the role in multiple inflammatory pathways. Multiple-hit etiology of primary biliary cholangitis (PBC) and evolving immune response at various stages of the disease includes involvement of Gal-3 in PBC pathogenesis. In this study we aimed to clarify the role of Gal-3 in Novosphingobium aromaticivorans (N. aromaticivorans) induced biliary disease. Autoimmune cholangitis was induced in mice by two intra-peritoneal injections of N. aromaticivorans within 2 weeks. The role of Gal-3 was evaluated by using Lgals3-/-mice and mice treated with Gal-3 inhibitor. The histological and serological parameters of disease, phenotype of dendritic, NK, NKT, and T cells and inflammasome expression were evaluated. Marked attenuation of the disease in Lgals3-/-and Gal-3 inhibitor, DAVANAT®, treated mice is manifested by the absence of bile duct damage, granulomas and fibrosis. Liver infiltrates of N. aromaticivorans infected wild type mice had higher incidence of pro-inflammatory macrophages, dendritic cells, NK, NKT, and T cells. Lgals3 deletion and treatment with Gal-3 inhibitor reduced inflammatory mononuclear cell infiltrate, expression of NLRP3 inflammasome in the liver infiltrates and interleukin-1β (IL-1β) production in the livers of N. aromaticivorans infected mice. In vitro stimulation of wild type peritoneal macrophages with N. aromaticivorans caused increased NLRP3 expression, caspase-1 activity and IL-1β production compared with Lgals3-/-cells. Our data highlight the importance of Gal-3 in promotion of inflammation in N. aromaticivorans induced PBC by enhancing the activation of NLRP3 inflammasome and production of IL-1β and indicate Gal-3 as possible therapeutical target in autoimmune cholangitis. Galectin-3 appears involved in inflammatory response to gut commensal leading to PBC. © 2019 Arsenijevic, Milovanovic, Stojanovic, Djordjevic, Stanojevic, Jankovic, Vojvodic, Arsenijevic, Lukic and Milovanovic.

Gal-3 has the role in multiple inflammatory pathways. Multiple-hit etiology of primary biliary cholangitis (PBC) and evolving immune response at various stages of the disease includes involvement of Gal-3 in PBC pathogenesis. In this study we aimed to clarify the role of Gal-3 in Novosphingobium aromaticivorans (N. aromaticivorans) induced biliary disease. Autoimmune cholangitis was induced in mice by two intra-peritoneal injections of N. aromaticivorans within 2 weeks. The role of Gal-3 was evaluated by using Lgals3-/-mice and mice treated with Gal-3 inhibitor. The histological and serological parameters of disease, phenotype of dendritic, NK, NKT, and T cells and inflammasome expression were evaluated. Marked attenuation of the disease in Lgals3-/-and Gal-3 inhibitor, DAVANAT®, treated mice is manifested by the absence of bile duct damage, granulomas and fibrosis. Liver infiltrates of N. aromaticivorans infected wild type mice had higher incidence of pro-inflammatory macrophages, dendritic cells, NK, NKT, and T cells. Lgals3 deletion and treatment with Gal-3 inhibitor reduced inflammatory mononuclear cell infiltrate, expression of NLRP3 inflammasome in the liver infiltrates and interleukin-1β (IL-1β) production in the livers of N. aromaticivorans infected mice. In vitro stimulation of wild type peritoneal macrophages with N. aromaticivorans caused increased NLRP3 expression, caspase-1 activity and IL-1β production compared with Lgals3-/-cells. Our data highlight the importance of Gal-3 in promotion of inflammation in N. aromaticivorans induced PBC by enhancing the activation of NLRP3 inflammasome and production of IL-1β and indicate Gal-3 as possible therapeutical target in autoimmune cholangitis. Galectin-3 appears involved in inflammatory response to gut commensal leading to PBC. © 2019 Arsenijevic, Milovanovic, Stojanovic, Djordjevic, Stanojevic, Jankovic, Vojvodic, Arsenijevic, Lukic and Milovanovic.

Background: The immune response in patients with melanoma is an important focus of research due to the tumor's resistance and immunotherapy possibilities. IL-27 is one of the cytokines with antitumor properties. The role of IL-27 in the pathogenesis of melanoma is still unclear. The aim of this study was to examine the association between serum IL-27 levels and the clinical parameters of melanoma patients. Methods: The IL-27 concentration was determined by commercial ELISA in serum samples from melanoma patients (n=72) and healthy control subjects (n=44). Patients were classified according to AJCC clinical stage, TNM stage, the length of progression-free interval (PFI) and the extent of the disease (localized or widespread). Results: Average IL-27 values were increased in patients with early stages of melanoma compared to patients with terminal stages and control values. The highest IL-27 concentration was found in stage IIa. Patients in stages III and IV had significantly lower values of IL-27 compared to control. Patients with localized melanoma and shorter PFI had insignificantly increased IL-27 levels compared to patients with widespread disease and longer PFI. Patients with metastatic disease and stage TNM4 had significantly lower average IL-27 values compared to control. Patients with high production of IL-27 (>1000 pg/mL) were most numerous in IIa AJCC stage, with initial tumor size TNM2 and in the group of patients with localized disease. Conclusions: High levels of IL-27 in patients with melanoma are associated with the initial stages and localized disease. © 2016 Jelena Pantic Bisevac et al.

Background: The immune response in patients with melanoma is an important focus of research due to the tumor's resistance and immunotherapy possibilities. IL-27 is one of the cytokines with antitumor properties. The role of IL-27 in the pathogenesis of melanoma is still unclear. The aim of this study was to examine the association between serum IL-27 levels and the clinical parameters of melanoma patients. Methods: The IL-27 concentration was determined by commercial ELISA in serum samples from melanoma patients (n=72) and healthy control subjects (n=44). Patients were classified according to AJCC clinical stage, TNM stage, the length of progression-free interval (PFI) and the extent of the disease (localized or widespread). Results: Average IL-27 values were increased in patients with early stages of melanoma compared to patients with terminal stages and control values. The highest IL-27 concentration was found in stage IIa. Patients in stages III and IV had significantly lower values of IL-27 compared to control. Patients with localized melanoma and shorter PFI had insignificantly increased IL-27 levels compared to patients with widespread disease and longer PFI. Patients with metastatic disease and stage TNM4 had significantly lower average IL-27 values compared to control. Patients with high production of IL-27 (>1000 pg/mL) were most numerous in IIa AJCC stage, with initial tumor size TNM2 and in the group of patients with localized disease. Conclusions: High levels of IL-27 in patients with melanoma are associated with the initial stages and localized disease. © 2016 Jelena Pantic Bisevac et al.

Background: Diagnosis of acute appendicitis (AA) and decisions about its treatment remain among the most common dilemmas of pediatric surgical teams. Monitoring of immune response may be of importance for this purpose. Our aim was to measure and analyze serum and peritoneal fluid cytokines, in children who had undergone surgery for suspected AA. Methods: Prospective investigation of serum and peritoneal fluid cytokine values was performed in 127 consecutive patients. According to the pathohistological findings, patients were divided into three groups: normal/early, uncomplicated and complicated AA. Determination of cytokine concentrations for 20 different cytokines was done using a commercial flow cytometry kit: Human Inflammation 20 plex BMS 819. Results: Statistically significant differences in serum cytokine values between pathohistological groups were found for IP-10, MIP-1α and IL-10. Preoperative cut-off values of IP-10, MIP-1α and IL-10 between groups were obtained using ROC curve analysis. Positive correlations between serum and peritoneal concentrations were recorded for most of the analyzed cytokines. Conclusion: IP-10, MIP-1α and IL-10 showed potential in assessment of AA in children. Confirmatory studies with a larger number of patients are required to prove reliability of these biomarkers. © 2019 The Author(s).